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ABSTRACT: Objective
The micro RNAs (miRNAs) and their target mRNAs are differentially expressed in various immune-mediated cells. Here, we investigated the role of Mir223 and sphingosine-1-phosphate receptor 1 (S1pr1) in the pathogenesis of systemic lupus erythematosus.Methods
We analyzed miRNA and mRNA profiling data of CD4+ splenic T cells derived from MRL/MpJ-Faslpr /J mice. We performed 3' untranslated region (UTR) luciferase reporter gene assay using human umbilical vein endothelial cells (HUVECs). We generated the B6-Mir223 -/- Faslpr/lpr mice and the lupus phenotypes were analyzed.Results
In CD4+ splenic T cells, we identified upregulation of miR-223-3p and downregulation of the possible target, S1pr1 by RNA sequencing of MRL/MpJ-Faslpr /J mice. The transfection with miR-223-3p mimic significantly suppressed a luciferase activity in HUVEC treated with a Lentivirus vector containing 3' UTR of S1pr1. The mRNA levels of S1pr1 were significantly decreased after miR-223-3p overexpression. In B6-Mir223 -/- Faslpr/lpr mice, the proportion of CD3+ T cells, CD3+CD4-CD8- cells, B cells, plasma cells, and S1PR1+CD4+ T cells in the spleen was significantly increased compared with that in B6-Mir223 +/+ Faslpr/lpr mice by flow cytometry. B6-Mir223 -/- Faslpr/lpr mice demonstrated the elevation of glomerular and renal vascular scores associated with enhanced intraglomerular infiltration of S1PR1+CD4+ T cells.Conclusion
Unexpectedly, the deletion of Mir223 exacerbated the lupus phenotypes associated with increased population of S1PR1+CD4+ T in spleen and the enhanced infiltration of S1PR1+CD4+ T cells in inflamed kidney tissues, suggesting compensatory role of Mir223 in the pathogenesis of lupus nephritis.
SUBMITTER: Hiramatsu-Asano S
PROVIDER: S-EPMC7871001 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Hiramatsu-Asano Sumie S Sunahori-Watanabe Katsue K Zeggar Sonia S Katsuyama Eri E Mukai Tomoyuki T Morita Yoshitaka Y Wada Jun J
Frontiers in immunology 20210126
<h4>Objective</h4>The micro RNAs (miRNAs) and their target mRNAs are differentially expressed in various immune-mediated cells. Here, we investigated the role of <i>Mir223</i> and sphingosine-1-phosphate receptor 1 (<i>S1pr1</i>) in the pathogenesis of systemic lupus erythematosus.<h4>Methods</h4>We analyzed miRNA and mRNA profiling data of CD4<sup>+</sup> splenic T cells derived from MRL/MpJ-<i>Fas<sup>lpr</sup></i> /J mice. We performed 3' untranslated region (UTR) luciferase reporter gene ass ...[more]